A5090472903- RNA and protein synthesis mechanisms
- DNA and Nucleic Acid Chemistry
- Genomics and Chromatin Dynamics
- Protein Structure and Dynamics
- DNA Repair Mechanisms
- Epigenetics and DNA Methylation
- Enzyme Structure and Function
- Advanced biosensing and bioanalysis techniques
- Bacterial Genetics and Biotechnology
- RNA modifications and cancer
- Bacteriophages and microbial interactions
- Long-Term Effects of COVID-19
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Scientific Computing and Data Management
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Exercise and Physiological Responses
- Spectroscopy and Quantum Chemical Studies
- Escherichia coli research studies
- RNA Interference and Gene Delivery
- Redox biology and oxidative stress
- Diffusion and Search Dynamics
- Cancer-related gene regulation
- CRISPR and Genetic Engineering
- Research Data Management Practices
Universitat de Barcelona
2022-2024
Institute for Research in Biomedicine
2015-2024
Universitat Politècnica de Catalunya
2011-2019
Barcelona Supercomputing Center
2011-2018
FC Barcelona
2018
University of Sheffield
2009-2012
There is increasing evidence for the presence of an alternative code imprinted in genome that might contribute to gene expression regulation through indirect reading mechanism. In mammals, components this coarse-grained regulatory mechanism include chromatin structure and epigenetic signatures, where d(CpG) nucleotide steps are key players. We report a comprehensive experimental theoretical study provides detailed description their physical characteristics impact cytosine methylation on...
We present a systematic study of the long-timescale dynamics Drew–Dickerson dodecamer (DDD: d(CGCGAATTGCGC)2) prototypical B-DNA duplex. Using our newly parameterized PARMBSC1 force field, we describe conformational landscape DDD in variety ionic environments from minimal salt to 2 M Na+Cl− or K+Cl−. The sensitivity simulations use different solvent and ion models is analyzed detail using multi-microsecond simulations. Finally, an extended (10 μs) simulation used characterize slow infrequent...
We have made a detailed study of one the most surprising sources polymorphism in B-DNA: high twist/low twist (HT/LT) conformational change d(CpG) base pair step. Using extensive computations, complemented with database analysis, we were able to characterize step all possible tetranucleotide environment. found that is coupled BI/BII transitions, and, quite surprisingly, slide neighboring Unexpectedly, penetration cations into minor groove seems be key element promoting transitions. The...
Molecular dynamics simulation (MD) is, just behind genomics, the bioinformatics tool that generates largest amounts of data, and is using amount CPU time in supercomputing centres. MD trajectories are obtained after months calculations, analysed situ, practice forgotten. Several projects to generate stable trajectory databases have been developed for proteins, but no equivalence exists nucleic acids world. We present here a novel database system store analyses acids. The initial data set...
Accumulating evidence suggests that autonomic dysfunction and persistent systemic inflammation are common clinical features in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) long COVID. However, there is limited knowledge regarding their potential association with circulating biomarkers illness severity these conditions.
Cytosine methylation is one of the most important epigenetic marks that regulate process gene expression. Here, we have examined effect DNA on nucleosomal stability using molecular dynamics simulations and elastic deformation models. We found CpG steps destabilizes nucleosomes, especially when these are placed in sites where minor groove faces histone core. The larger stiffness methylated a crucial factor behind decrease nucleosome stability. Methylation changes positioning phasing DNA,...
Abstract New hardware, massively parallel and graphical processing unit‐based computers in particular, has boosted molecular simulations to levels that would be unthinkable just a decade ago. At the classical level, it is now possible perform atomistic with systems containing over 10 million atoms collect trajectories extending millisecond range. Such achievements are moving biosimulations into mainstream of structural biology research, complementary experimental studies. The drawback this...
We present a physics-based machine learning approach to predict in vitro transcription factor binding affinities from structural and mechanical DNA properties directly derived atomistic molecular dynamics simulations. The method is able obtained with techniques as different uPBM, gcPBM HT-SELEX an excellent performance, much better than existing algorithms. Due its nature, the can be extended epigenetic variants, mismatches, mutations, or any non-coding nucleobases. When complemented...
Abstract Traditional mesoscopic models of DNA flexibility use a reductionist-local approach, which assumes that the can be expressed as local harmonic movements (at base-pair step level) in helical space, ignoring multimodality and correlations movements, have reality large impact modulating movements. We present new multimodal-harmonic correlated model, takes both contributions into account, providing, with small computational cost, results an unprecedented global quality. The accuracy this...
The mitochondrial genome (mtDNA) is assembled into nucleo-protein structures termed nucleoids and maintained differently compared to nuclear DNA, the involved molecular basis remaining poorly understood. In yeast (Saccharomyces cerevisiae), mtDNA a ∼80 kbp linear molecule Abf2p, double HMG-box protein, packages maintains it. protein binds DNA in non-sequence-specific manner, but displays distinct 'phased-binding' at specific sequences containing poly-adenine tracts (A-tracts). We present...
This letter illustrates the opinion of molecular dynamics (MD) community on need to adopt a new FAIR paradigm for use simulations. It highlights necessity collaborative effort create, establish, and sustain database that allows findability, accessibility, interoperability, reusability simulation data. Such development would democratize field significantly improve impact MD simulations life science research. will transform our working paradigm, pushing frontier. We invite you support...
In eukaryotic organisms, DNA is packaged into chromatin structure, where most of wrapped nucleosomes. compaction and nucleosome positioning have clear functional implications, since they modulate the accessibility genomic regions to regulatory proteins. Despite intensive research effort focused in this area, rules defining location still remain elusive.Naked (histone-free) nucleosomal from yeast were digested by microccocal nuclease (MNase) sequenced genome-wide. MNase cutting preferences...
Tudor-interacting repair regulator (TIRR) is an RNA-binding protein and a negative of the DNA-repair factor p53-binding 1 (53BP1). In non-damage conditions, TIRR bound to 53BP1. After DNA damage, 53BP1 dissociate, binds chromatin at double-strand break (DSB) promote non-homologous end joining (NHEJ)-mediated repair. However, exact mechanistic details this dissociation after damage are unknown. Increasing evidence has implicated RNA as crucial in response (DDR). Here, we show that can...
Abstract Human mitochondrial DNA (h-mtDNA) codes for 13 subunits of the oxidative phosphorylation pathway, essential route that produces ATP. H-mtDNA transcription and replication depends on factor TFAM, which also maintains compacts this genome. It is well-established TFAM activates mtDNA promoters LSP HSP1 at control region where regulatory elements cluster. Previous studies identified still uncharacterized, additional binding sites downstream from slightly similar to LSP, namely sequences...
We present Nucleosome Dynamics, a suite of programs integrated into virtual research environment and created to define nucleosome architecture dynamics from noisy experimental data. The package allows both the definition architectures detection changes in nucleosomal organization due cellular conditions. Results are displayed context genomic information thanks different visualizers browsers, allowing user holistic, multidimensional view genome/transcriptome. shows good performance for...
Abstract We demonstrate that nucleosomes placed in the gene body can be accurately located from signal decay theory assuming two emitters at beginning and end of genes. These generated wave signals phase (leading to well defined nucleosome arrays) or antiphase fuzzy architectures). found first (+1) last (-last) are contiguous regions signaled by transcription factor binding sites unusual DNA physical properties hinder wrapping. Based on these analyses, we developed a method combines Machine...